FRG: Collaborative Research: Variational multiscale approaches to biomolecular structure, dynamics and transport

21世纪生物科学的一个主要特征将是它从一门现象学和描述性学科向一门定量和预测性学科的转变。在生物学研究中，数学驱动的进步带来了革命性的机遇。在过去的几十年里，对自组织生物分子系统（如HIV病毒、分子马达和阿尔茨海默病中的蛋白质）的实验探索一直是科学发现和创新的主导力量。然而，自组织生物系统中复杂性的出现，由于其过高的维数，对其定量描述提出了根本性的挑战。这个重点研究小组（FRG）将提供一个平台，由密歇根州立大学、威斯康星大学麦迪逊分校和宾夕法尼亚州立大学的主要研究人员领导，他们将协同合并他们在理论建模、科学计算和数学分析方面的专业知识，用于生物分子系统的定量描述。由于异常庞大的数据集，该研究解决了自组织生物分子系统在结构、功能和动力学方面的重大挑战。这些挑战是通过引入新的变分多尺度模型来解决的，该模型通过对水生/膜环境的宏观连续描述和对生物分子的微观离散描述来降低维数和自由度。此外，为了进一步降低超大生物分子系统的维数，研究人员引入了一种基于密度簇动力学的粗粒度方法，该方法在分子动力学模拟中提取稳定流形。该FRG项目为生物分子系统的海量数据管理、降维、计算机模拟、理论建模和数学分析提供了创新的新方法。该项目是推动生物科学定量转型的及时努力，它将导致数学和生物科学的新兴领域。特别是，通过积极追求前沿研究和在这一新兴跨学科领域合作培养新一代数学家，提议的努力将显著加强美国研究人员在数学分子生物科学领域的领导作用。每年将在密歇根州立大学（一年级）、威斯康星州（二年级）和宾夕法尼亚州立大学（三年级）举行三次研讨会和国际会议，以加强合作，扩大社会影响。

A major feature of biological science in the 21st Century will be its transition from a phenomenological and descriptive discipline to a quantitative and predictive one. Revolutionary opportunities have emerged for mathematically driven advances in biological research. Experimental exploration of self-organizing biomolecular systems, such as HIV viruses, molecular motors and proteins in Alzheimer's disease, has been a dominating driven force in scientific discovery and innovation in the past few decades. However, the emergence of complexity in self-organizing biological systems poses fundamental challenges to their quantitative description because of the excessively high dimensionality. This Focused Research Group (FRG) will provide a platform, led by leading researchers from Michigan State University, University of Wisconsin-Madison and Pennsylvania State University, who will synergistically merge their expertise in theoretical modeling, scientific computing and mathematical analysis, for quantitative descriptions of biomolecular systems. The research addresses grand challenges in the structure, function and dynamics of self-organizing biomolecular systems due to exceptionally massive data sets. These challenges are tackled through the introduction of new variational multiscale models, which reduces the dimensionality and number of degrees of freedom by a macroscopic continuum description of the aquatic/membrane environment, and a microscopic discrete description of biomolecules. Additionally, to further reduce the dimensionality of excessively large biomolecular systems, the investigators introduce a coarse-grained approach based on the density cluster dynamics which extracts stable manifolds in molecular dynamics simulations. This FRG project offers innovative new approaches to the massive data management, dimensionality reduction, computer simulation, theoretical modeling and mathematical analysis of biomolecular systems.This project is a timely effort to promote the quantitative transition of biological science, which will lead to emerging new fields in both mathematical and biological sciences. In particular, the proposed effort will significantly strengthen the leading role that the U.S. researchers can play in mathematical molecular biosciences by aggressively pursuing cutting-edge research and collaboratively training a new generation of mathematicians in this emerging interdisciplinary field. Three annual workshops and international meeting will be held in Michigan State (Year 1), Wisconsin (Year 2) and Penn State (Year 3) to strengthen the collaboration and extend the societal impact.